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产前抑郁及抗抑郁治疗对胎盘基因表达的影响。

The effects of antenatal depression and antidepressant treatment on placental gene expression.

作者信息

Olivier Jocelien D A, Åkerud Helena, Skalkidou Alkistis, Kaihola Helena, Sundström-Poromaa Inger

机构信息

Department of Women's and Children's Health, Uppsala University Uppsala, Sweden ; Department of Behavioral Physiology, University of Groningen Groningen, Netherlands ; Department of Medicine, Centre for Gender Medicine, Karolinska Institute Stockholm, Sweden.

Department of Women's and Children's Health, Uppsala University Uppsala, Sweden.

出版信息

Front Cell Neurosci. 2015 Jan 13;8:465. doi: 10.3389/fncel.2014.00465. eCollection 2014.

Abstract

The effects of antenatal depression and antidepressant treatment during pregnancy on both mother and child are vigorously studied, but the underlying biology for these effects is largely unknown. The placenta plays a crucial role in the growth and development of the fetus. We performed a gene expression study on the fetal side of the placenta to investigate gene expression patterns in mothers with antenatal depression and in mothers using antidepressant treatment during pregnancy. Placental samples from mothers with normal pregnancies, from mothers with antenatal depression, and from mothers using antidepressants were collected. We performed a pilot microarray study to investigate alterations in the gene expression and selected several genes from the microarray for biological validation with qPCR in a larger sample. In mothers with antenatal depression 108 genes were differentially expressed, whereas 109 genes were differentially expressed in those using antidepressants. Validation of the microarray revealed more robust gene expression differences in the seven genes picked for confirmation in antidepressant-treated women than in depressed women. Among the genes that were validated ROCK2 and C12orf39 were differentially expressed in both depressed and antidepressant-treated women, whereas ROCK1, GCC2, KTN1, and DNM1L were only differentially expressed in the antidepressant-treated women. In conclusion, antenatal depression and antidepressant exposure during pregnancy are associated with altered gene expression in the placenta. Findings on those genes picked for validation were more robust among antidepressant-treated women than in depressed women, possibly due to the fact that depression is a multifactorial condition with varying degrees of endocrine disruption. It remains to be established whether the alterations found in the gene expression of the placenta are found in the fetus as well.

摘要

孕期产前抑郁及抗抑郁药物治疗对母亲和孩子的影响得到了深入研究,但这些影响背后的生物学机制仍 largely 未知。胎盘在胎儿的生长发育中起着关键作用。我们对胎盘的胎儿侧进行了基因表达研究,以调查产前抑郁母亲及孕期使用抗抑郁药物治疗的母亲的基因表达模式。收集了正常妊娠母亲、产前抑郁母亲及使用抗抑郁药物母亲的胎盘样本。我们进行了一项先导性微阵列研究,以调查基因表达的变化,并从微阵列中选择了几个基因,在更大的样本中用 qPCR 进行生物学验证。产前抑郁母亲中有 108 个基因差异表达,而使用抗抑郁药物的母亲中有 109 个基因差异表达。微阵列的验证显示,在抗抑郁药物治疗的女性中挑选用于确认的 7 个基因的基因表达差异比抑郁女性中更显著。在经验证的基因中,ROCK2 和 C12orf39 在抑郁和抗抑郁药物治疗的女性中均差异表达,而 ROCK1、GCC2、KTN1 和 DNM1L 仅在抗抑郁药物治疗的女性中差异表达。总之,产前抑郁和孕期暴露于抗抑郁药物与胎盘基因表达改变有关。在抗抑郁药物治疗的女性中,那些挑选用于验证的基因的研究结果比抑郁女性中更可靠,这可能是因为抑郁是一种多因素疾病,存在不同程度的内分泌紊乱。胎盘基因表达中发现的改变是否也存在于胎儿中仍有待确定。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4acc/4292720/44d3fce0b049/fncel-08-00465-g0001.jpg

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